The primary objective of this proposal is to investigate some chemical and physical properties of certain lipid and protein components of the synaptic membrane and other neural components from the standpoint of their possible involvement in opiate binding and action. The impetus for this study stemmed from the observation that opiates bind strongly to phosphatidyl serine; and, since this lipid may play an important role in the activation of a number of membranous enzymes as well as in Ca2+ and neurotransmitter affinity to the synaptic membrane, a major effort is devoted to a study of its role in membrane function and opiate binding. An attempt will be made to determine whether the lipid may be a component of the opiate pharmacophore (receptor), under intensive study by various investigators. Specific aims are to 1) study phosphatidyl serine-opiate interactions with the use of fluorescence and NMR spectroscopy; 2) investigate opiate binding to various species of phosphatidyl serine isolated from brain tissue; 3) study opiate binding to monolayer, micellar and other complexes of the lipids and membranous proteins and enzymes; 4) study opiate binding after selective modification of phosphatidyl serine in intact synaptic membranes. It is hoped that such studies will be of value in understanding not only the mechanisms by which opiates act on the brain, but also the structural and functional organization of the synaptic membrane.